CYTOTOXIC EFFECT OF CYTOKINES ON MURINE COLON-CARCINOMA CELLS INVOLVES TNF-MEDIATED APOPTOSIS

We have studied the cytotoxic effect of TNF-alpha on C-26 murine colon carcinoma cells in vitro, Treatment with TNF-alpha alone did not resu lt in any demonstrable cytotoxicity. However, when combined with IFN-g amma, the cytotoxic effect of TNF-alpha was enhanced in a dose-depende nt manner. An agonistic TNF-R1 specific antibody and recombinant human TNF-alpha both exerted a cytotoxic effect when combined with IFN-gamm a, suggesting that the cytotoxicity was mediated through the TNF-R1, T he cytotoxicity was associated with production of nitric oxide without any direct involvement in the cytotoxic effect. At the ultrastructura l level, treated cells displayed a typical apoptotic morphology which was not accompanied by internucleosomal cleavage of DNA as shown by co nventional electrophoresis. (C) 1997 Academic Press.